TCL-1 and MTCP-1 are members of a novel family of human genes that are involved in T-ell malignancies and lymphoid proliferation and/or survival. These genes code for proteins of about 14 kDa molecular weight, that share 41% identical amino acid residues. Human TCL-1 and MTCP-1 and mouse TCL-1 have been expressed in E. coli and purified in milligram quantities for structural analysis. The crystal structure of MTCP-1 has been determined at 2.0 A resolution. The structure is a unique 8-stranded beta barrel with one short helix. The structure of TCL- 1 is very similar with a root mean square deviation of 1.7 angstrom on all common Calpha atoms. The structural information is being used for site- directed mutagenesis, and to design peptide analogs of surface regions of the proteins as potential inhibitors of oncogene function. Mutant forms of TCL-1 and MTCP-1 will be expressed, characterized and analyzed structurally in comparison to the wild type protein. Interacting proteins and other potential ligands of TCL-1 and MTCP-1 will be studied by crystallography and biochemical methods. The structures and functions of TCL-1 and MTP-1 proteins will be compared. Inhibitors of TCL-1 and MTCP-1 have potential for treatment for low-grade T-cell lymphomas and leukemias.